Treating Prostatitis Effectively

A Challenge for Clinicians

Nhuan Nguyen, PharmD, MBA, CHE

US Pharmacist. 2014;39(4):35-41.

Abstract and Introduction

Abstract

Prostatitis, which affects 5% to 9% of males and occurs mostly in middle age, is classified based on signs and symptoms, with urinary urgency, frequency, and pain typical in nearly all categories. Most physicians are not familiar with prostatitis, particularly chronic prostatitis associated with chronic pelvic pain syndrome (CP/CPPS). Accordingly, patients are often misdiagnosed and receive ineffective treatment, resulting in poor quality of life. CP/CPPS is challenging to treat, as its causes are not clearly defined and the antibiotics used for therapy have low effective rates. Clinical pharmacists can contribute significantly to patient care by advising physicians and other medical professionals regarding drug efficacy, adverse drug reactions, and drug interactions, and by assisting in the selection of optimal antibiotics and/or treatment regimens for prostatitis.

Introduction

Prostatitis (inflammation of the prostate gland), which occurs in 5% to 9% of males aged 18 years and older, most often develops in middle age.^[1] In the early 1990s, prostatitis accounted for about 1% and 8% of office visits to family practitioners and urologists, respectively.^[1]

In most cases, patients with prostatitis experience urinary urgency, frequency, and pain, all of which significantly impact quality of life (QOL).^[1–8] It is believed that the QOL of patients with prostatic pain is similar to that of patients with acute myocardial infarction, unstable angina, or active Crohn's disease.^[1] A 2009 survey of 556 primary care physicians in Boston, Chicago, and Los Angeles found that only 62% saw patients for prostatitis; surprisingly, 48% of physicians surveyed were not familiar with prostatitis and 16% were unfamiliar with chronic prostatitis associated with chronic pelvic pain syndrome (CP/CPPS).^[4] Consequently, the diagnosis and effective treatment of prostatitis, especially CP/CPPS, pose a challenge for clinicians.

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Table 1. NIH Classification of Prostatitis
Category	Signs and Symptoms
I	Urinary frequency, urgency, dysuria; altered smell, color, or consistency of urine. Prostate enlarged and tender. Acute severe pain (suprapubic, perineal, external genital) caused by prostate inflammation. Systemic signs and symptoms caused by bacteriuria and pyuria: fever, chills and rigors, arthralgia and myalgia, N/V, signs of sepsis
II	Irritative urination related to recurrent UTI. Prostate normal or enlarged, tender, possibly nodular. CPP: low-grade fever with low back or pelvic discomfort with perineal, testicular, occasionally distal penile pain. Increased EPS pH
III	Irritative urination with no detection of UTI for ≥3 mo. Prostate normal or enlarged, but not tender. CPP: perineal, lower abdominal, penile, testicular, rectal and lower back, ejaculatory pain. Inflammatory CP/CPPS: leukocytes in EPS, post–prostatic massage urine, or semen
IV	No symptoms, but evidence of prostate inflammation

CP/CPPS: chronic prostatitis associated with chronic pelvic pain syndrome; CPP: chronic pelvic pain; EPS: expressed prostatic secretions; NIH: National Institutes of Health; N/V: nausea and vomiting; UTI: urinary tract infection.
Source: References 1–8.

Table 2. Prostatitis Diagnosis
Category	Diagnostic Methods
I	Thorough medical history, physical examination, and symptom evaluation Urinalysis, urine culture, and sensitivity Blood culture
II	Diagnostic methods used for category I, plus: Ejaculate culture Leukocyte detection in EPS or post–prostatic massage urine
III	Diagnostic methods used for category I, plus: Leukocyte detection in EPS or post–prostatic massage urine Psychological evaluation Diagnosis of exclusion
IV	Results from other urologic evaluations (PSA level, prostate biopsy, BPH, OAB, infertility)

BPH: benign prostatic hyperplasia; EPS: expressed prostatic secretion; OAB: overactive bladder; PSA: prostate-specific antigen.
Sources: References 1–3, 5, 7, 8, 13, 14.

Table 3. Treatment Regimens for ABP and CBP
Category	Empiric Regimen	Considerations
ABP (uncomplicated)	Primary: ciprofloxacin 500 mg po q12h, or levofloxacin 500–750 mg po q24h. Alternative: TMP-SMX DS one tablet po q12h	Duration: 14 days; may extend to 4 wk. Adjust ciprofloxacin, levofloxacin, or TMP-SMX dosage in renal deficiency. Urine culture 2 wk and 4 wk after therapy completion
ABP (uncomplicated, with risk of STD due to N gonorrhoeae, C trachomatis)	Primary: ceftriaxone 250 mg IM, or cefixime 400 mg × 1 dose po plus doxycycline 100 mg po q12h × 14 days, or azithromycin po 500 mg q24h × 14 days	Fluoroquinolones no longer used for gonococcal infection. Urine test for N gonorrhoeae, C trachomatis
ABP (complicated by bacteremia and/or prostatic abscess)	Primary: ciprofloxacin 400 mg IV q12h, or levofloxacin 500 mg IV q24h. Alternative: ceftriaxone 1–2 g IV q24h plus levofloxacin 500–750 mg po q24h, or ertapenem 1 g IV q24h, or piperacillin-tazobactam 3.375 g IV q6h	Duration: 4 wk. Ultrasound or CT scan to confirm abscess. IV switch to oral when blood culture negative or abscess drained
CBP	Primary: ciprofloxacin 500 mg po q12h, or levofloxacin 500–750 mg po q24h. Alternative: doxycycline 100 mg po q24h, or TMP-SMX DS one tablet po q12h	Duration: 1–3 mo

ABP: acute bacterial prostatitis; C trachomatis: Chlamydia trachomatis; CBP: chronic bacterial prostatitis; DS: double strength; N gonorrhoeae: Neisseria gonorrhoeae; STD: sexually transmitted disease; TMP-SMX: trimethoprim-sulfamethoxazole.
Source: References 1–3, 5, 15–26.

Table 4. Treatment Regimens for CP/CPPS
Symptoms	Regimen	Indication/Consideration
Urinary urgency, frequency, dysuria	Alpha-blocker: tamsulosin 0.4 mg po daily; alfuzosin 10 mg po daily for 1–2 wk Anticholinergic: tolterodine 2 mg po bid, or 2 mg po daily if used concurrently with ketoconazole, clarithromycin, and/or ritonavir. Antispasmodic: oxybutynin 5 mg po tid-qid (IR), or 5–10 mg daily (ER); max 30 mg daily	Tamsulosin: improvement in symptoms of BPH, BOO. Alfuzosin: ureteral stone expulsion (discontinue after successful expulsion). Tolterodine and oxybutynin: improvement in symptoms of OAB (frequency, urgency). Oxybutynin: relaxation of bladder smooth muscle, which decreases urgency and frequency
Psychosocial: depression, anxiety/stress, history of sexual or other physical abuse	Psychological counseling, CBT, and antidepressant (e.g., nortriptyline 25 mg po tid-qid to 150 mg daily)	Depression treatment. Do not adjust dosage until after 1st wk
Prostate pain (trauma, infection, inflammation)	Injury, inflammation: quercetin, bee pollen	Improvement in CP/CPPS symptoms and inflammation and reduction in oxidative stress
Infection due to gram-negative bacilli and gram-positive enterococci found in midstream urine or post–massage urine at low counts or localized to EPS	Antibiotics used to treat CBP	If no response, no further antibiotic treatment warranted
Neurologic symptoms	Pregabalin: 75 mg po bid, increase to 150 mg bid if tolerated; max 300 mg bid. Gabapentin: 300–3,600 mg po daily in divided doses. Nortriptyline: 10–25 mg po qhs initially, then increase gradually by 25 mg/day per wk if tolerated; max 75 mg/day. Amitriptyline: 25–50 mg po daily, gradually increase to 100–300 mg/day. Acupuncture may be used	Pregabalin: fibromyalgia. Gabapentin (unlabeled use): neuropathic pain. Both: Adjust dosage in renal deficiency
Tenderness in pelvic muscles	Physical therapy for pelvic floor	Strengthening of pelvic muscles

BOO: bladder outlet obstruction; BPH: benign prostatic hyperplasia; CBP: chronic bacterial prostatitis; CBT: cognitive behavioral therapy; CP/CPPS: chronic prostatitis associated with chronic pelvic pain syndrome; EPS: expressed prostate secretions; ER: extended-release; IR: immediate-release; max: maximum; OAB: overactive bladder.
Source: References 15, 22.

Table 5. Common Adverse Drug Reactions and Interactions
Agent	Reactions	Interactions
Ciprofloxacin	BBW: tendon rupture, potential risk of PN, muscle weakness related to MG. Nausea (3%), rash, abdominal pain (1%)	Risk X: Ciprofloxacin increases clozapine plasma levels. Avoid concurrent use with clozapine; alternatively, reduce clozapine dose
Levofloxacin	Chest pain (1%), edema (1%), HA (6%), insomnia (4%), dizziness (3%), rash (2%)	Risk X: Avoid combining with QTc-prolonging agents
TMP-SMX	Aseptic meningitis, chills, depression, HA, seizure (frequency not defined). Rare: SJS, hepatotoxicity, SLE	Risk X: Leucovorin calcium decreases therapeutic effects of TMP; methenamine increases toxicity of SMX
Ceftriaxone	Rash (2%), diarrhea (3%), eosinophilia (6%), thrombocytosis (5%), leukopenia (2%)	No risk X interaction
Doxycycline	IH, pericarditis, hypoglycemia, nausea (13%), vomiting (8%), diarrhea (3%), HA, neutropenia, thrombocytopenia	Risk X: Increases pimozide level; increases toxicity of retinoic acid derivatives and strontium ranelate
Azithromycin	Diarrhea, nausea (>10%); rash, abdominal pain, anorexia (2%-10%)	Risk X: Azithromycin increases QTc-prolonging effect of amiodarone, terfenadine
Ertapenem	CNS: confusional states and seizures. Increased seizure risk in patients with renal deficiency	Risk X: Avoid concurrent use with valproic acid and derivatives
Piperacillin-tazobactam	Diarrhea (11%), constipation (8%), insomnia, nausea (7%), agitation, pain, anxiety, dizziness, hypertension (1%), chest pain, edema, phlebitis (1%)	Risk X: Tetracycline decreases concentration of PNC; antibiotic may decrease BCG's effect
Tamsulosin	OH (6%-19%), headache (19–21%), dizziness (15%-17%), abnormal ejaculation (8%-18%), rhinitis (13%-18%)	Risk X: Enhances antihypertensive effect of alpha₁-blocker
Alfuzosin	Dizziness (6%), fatigue, headache (3%), abdominal pain, constipation, nausea, bronchitis, pharyngitis, sinusitis (1%-2%)	Risk X: Avoid concurrent use with alpha₁-blockers, CYP3A4 inhibitors, QTc-prolonging agents, protease inhibitors (increase alfuzosin level)
Tolterodine	Dry mouth (35%), headache (7%), dizziness (5%), abdominal pain (5%), constipation (7%), dysuria (2%), abnormal vision (2%)	Risk X: Avoid concurrent use with ipratropium, potassium chloride (enhances ulcerogenic effect), tiotropium (enhances anticholinergic effect)
Oxybutynin	Dizziness (4%-17%), drowsiness (2%-14%), xerostomia (29%-71%, dose-related), constipation (7%-15%), and nausea (2%-12%)	No risk X interactions
Pregabalin	PE (16%), dizziness (8%-45%), somnolence (4%-36%), ataxia (1%-30%), headache (5%-14%), tremor (11%), blurred vision (1%-12%), xerostomia (15%), tremor (11%), weight gain (11%)	Risk X: Avoid concurrent use with azelastine, paraldehyde, or thalidomide
Gabapentin	Dizziness (17%-28%), drowsiness (19%-21%), ataxia (1%-13%), fatigue (11%)	Risk X: Avoid concurrent use with azelastine or thalidomide (enhances CNS depressant effect)
Nortriptyline, amitriptyline	BBW: increased risk of suicidal thinking and behavior, MDD. CNS effects (agitation, confusion, dizziness, drowsiness, seizure, etc.). Arrhythmia, heart block, hypertension, OH (frequency not defined)	Risk X: Amitriptyline enhances arrhythmogenic effect of cisapride and anticholinergic effect of ipratropium. Linezolid and MAOIs enhance serotonergic effect of TCAs, leading to SS. TCAs enhance serotonergic effect of methylene blue, leading to SS

BBW: black box warning; BCG: bacillus Calmette-Guérin; CNS: central nervous system; HA: hemolytic anemia; IH: intracranial hypertension; MAOI: monoamine oxidase inhibitor; MDD: major depressive disorder; MG: myasthenia gravis; OH: orthostatic hypotension; PE: peripheral edema; PN: peripheral neuropathy; PNC: penicillin; SJS: Stevens-Johnson syndrome; SLE: systemic lupus erythematosus; SS: serotonin syndrome; TCA: tricyclic antidepressant; TMP-SMX: trimethoprim-sulfamethoxazole.
Source: Reference 15.